Knowledge of the range of diversity in a biological system may provide valuable insight into its functioning. Starting from this premise, we are studying 3 types of variation in the immune system. The first group of variants consists of immunoglobulins with gross structural lesions that are evidently results of errors in biosynthesis. Proteins to be studied include a crystallizable human myeloma protein with a hinge region deletion and structural variants of the murine myeloma protein, MOPC 315. Analysis of these variants may contribute to our understanding of the control of immunoglobulin gene expression. In addition, such variants provide unique material for studies of immunoglobulin function. The second type of variation is the normal expression of immunoglobulin (antibody) diversity, as manifest by the amino acid sequence of the variable region. We plan to study the structural variation in light chains that have the same constant domain as the light (lambda 2) chain of the myeloma protein MOPC 315. The amino acid sequences of the variable regions of these lambda 2 proteins will be compared with that of the MOPC 315 light chain. These studies should provide information on the general question of how antibody variability is generated. The third type of diversity to be investigated is the evolution of the immune response. Understanding the variations in the immune systems of different vertebrates groups may provide insight into the basic features of these systems, and thus enhance our understanding of the mammalian immune response. Aspects of the structure and function of immunoglobulins, lymphocytes, and complement components of the amphibian Rana catesbeiana, will be studied.